Prevalence of white matter hyperintensities is not elevated in a large sample of adolescents and young adults with bipolar disorder

Objective: The increased prevalence rate of white matter hyperintensities is one of the most consistently reported brain abnormalities in adults with bipolar disorder. However, findings in children and adolescents with bipolar disorder are less consistent. Prior studies have been constrained by small sample sizes and/or poor age- and sex-matching of healthy controls. We examined this topic in the largest sample of adolescents with bipolar disorder to date. Methods: T2-weighted 3-Tesla magnetic resonance imaging data were acquired for 83 adolescents with bipolar disorder diagnosed via the Kiddie Schedule for Affective Disorders and the Schizophrenia, Present and Lifetime version semi-structured interview and 64 age- and sex-matched healthy controls. All acquired scans were examined by neuroradiologists and the presence or absence of white matter hyperintensities was determined for each participant. Results: The prevalence of white matter hyperintensities did not differ between adolescents with bipolar disorder (13.3%) and controls (21.9%; χ2 = 1.90; p = 0.168). Conclusion: In contrast to the study hypothesis, the prevalence of white matter hyperintensities was not higher in adolescents with bipolar disorder than controls. The large sample size and good matching for age and sex bolster the reliability of this negative finding. Future studies are warranted to evaluate the prevalence, incidence, and predictors of white matter hyperintensities in early-onset bipolar disorder prospectively.

Neurobiology of bipolar disorders: a review of genetic components, signaling pathways, biochemical changes, and neuroimaging findings

Bipolar disorder (BD) is a chronic mental illness characterized by changes in mood that alternate between mania and hypomania or between depression and mixed states, often associated with functional impairment. Although effective pharmacological and non-pharmacological treatments are available, several patients with BD remain symptomatic. The advance in the understanding of the neurobiology underlying BD could help in the identification of new therapeutic targets as well as biomarkers for early detection, prognosis, and response to treatment in BD. In this review, we discuss genetic, epigenetic, molecular, physiological and neuroimaging findings associated with the neurobiology of BD. Despite the advances in the pathophysiological knowledge of BD, the diagnosis and management of the disease are still essentially clinical. Given the complexity of the brain and the close relationship between environmental exposure and brain function, initiatives that incorporate genetic, epigenetic, molecular, physiological, clinical, environmental data, and brain imaging are necessary to produce information that can be translated into prevention and better outcomes for patients with BD.

Optical coherence tomography findings in bipolar disorder: a preliminary receiver operating characteristic analysis on ganglion cell layer volume for diagnosis

Abstract Background Optical coherence tomography (OCT) has been recently used to investigate neuropsychiatric disorders. Objective The aim of this study was to compare the retinal nerve fiber layer thickness (RNFLT) and the ganglion cell layer (GCL) volume in patients with type 1 bipolar disorder (BPD1, diagnosed according to DSM 5) to the values in healthy controls. Methods Eighty consecutive outpatients with a diagnosis of euthymic BPD1 and 80 healthy controls were enrolled in the study. Following assessment with the Sociodemographic Data Form, Structured Clinical Interview for DSM-IV (SCID-I), Hamilton Depression Scale and Young Mania Evaluation Scale, both groups underwent Optical coherence tomography (OCT). Results The mean RNFL thickness and mean GCL volume were significantly lower in the BPD1 group than in the controls (p < 0.05). The GCL global value had a significant and independent effect in distinguishing the BPD1 patients from the controls. A cut-off value of 101 mm3 for global GCL volume was proposed to distinguish BPD1 patients from controls with a sensitivity of 87.5%. Discussion Lower values of GCL volume and RNFLT in patients suffering from BPD1 suggest that neurodegeneration may occur during the course of BPD and that this degeneration can be characterized in particular by a thinning of the GCL volume.

White matter volume is decreased in bipolar disorder at early and late stages / O volume da substância branca está reduzido tanto nos estágios iniciais quanto nos estágios avançados do transtorno bipolar

Abstract Introduction: Bipolar disorder (BD) is a debilitating mood condition that affects approximately 1.3% of people worldwide, although some studies report up to 3.9% lifetime prevalence and 4-6% in adults when broad diagnostic criteria are applied. Objective: To compare differences in total white matter (WM), corpus callosum (CC) and total gray matter (GM) volumes in patients with type I BD at early and late stages compared with controls. Methods: Fifty-five subjects were enrolled in this study protocol. The double case-control design included 14 patients with BD at early stage; 15 patients at late stage; and their respective matched controls (14 and 12 subjects). Results: CC and total WM volumes were significantly smaller in patients with BD at early and late stages vs. controls. There was no difference for total GM volume in the early stage group, but in patients at late stage total GM volume was significantly smaller than in controls. The total GM volume reduction in patients at late stage is in agreement with the neuroprogression theory of BD. The reduction of WM volumes in total WM and in the CC at early and late stages supports the possibility that an early demyelination process could occur underlying the clinical manifestation of BD. Conclusion: Our findings may direct to the investigation of WM abnormalities in populations at high risk to develop BD, perhaps as early biomarkers before the overt syndrome.

Resumo Introdução: O transtorno do humor bipolar (THB) é uma condição debilitante que afeta aproximadamente 1,3% das pessoas em todo o mundo, embora alguns estudos relatem uma prevalência acumulada de até 3,9% e de 4-6% em adultos quando os critérios diagnósticos mais abrangentes são aplicados. Objetivo: Comparar as diferenças nos volumes totais de substância branca (SB), corpo caloso (CC) e volume total de substância cinzenta (SC) em pacientes com THB tipo I em estágios iniciais e tardios em comparação com controles. Métodos: Cinquenta e cinco sujeitos foram incluídos neste protocolo de estudo. O desenho de caso com duplo controle incluiu 14 pacientes com THB em estágio inicial; 15 pacientes com THB em fase tardia; e seus respectivos controles correspondentes (14 e 12 sujeitos). Resultados: Os volumes do CC e total de SB foram significativamente menores nos pacientes com THB nos estágios iniciais e tardios vs. controles. Não houve diferença para o volume total de SC no grupo em estágio inicial, mas em pacientes em fase tardia o volume total de SC foi significativamente menor do que nos controles. A redução do volume total de SC em pacientes em fase tardia está de acordo com a teoria da neuroprogressão do THB. A redução dos volumes de SB em SB total e no CC em fases precoces e tardias suporta a possibilidade de que um processo de desmielinização precoce poderia ocorrer subjacente à manifestação clínica de THB. Conclusão: Nossos achados podem direcionar a investigação de anormalidades da SB em populações de alto risco para o desenvolvimento de THB, talvez como biomarcadores precoces antes da síndrome aberta.

Challenges and developments in research of the early stages of bipolar disorder

Recently, attention in the field of bipolar disorder (BD) has focused on prevention, including early detection and intervention, as these strategies have the potential to delay, lessen the severity, or even prevent full-blown episodes of BD. Although knowledge of the neurobiology of BD has advanced substantially in the last two decades, most research was conducted with chronic patients. The objective of this paper is to comprehensively review the literature regarding the early stages of BD, to explore recent discoveries on the neurobiology of these stages, and to discuss implications for research and clinical care. The following databases were searched: PubMed, PsycINFO, Cochrane Library, and SciELO. Articles published in English from inception to December 2015 were retrieved. Several research approaches were used, including examination of offspring studies, retrospective studies, prospective studies of clinical high-risk populations, and exploration of the progression after the first manic episode. Investigations with neuroimaging, cognition assessments, and biomarkers provide promising (although not definitive) evidence of alterations in the neural substrate during the at-risk stage. Research on BD should be expanded to encompass at-risk states and aligned with recent methodological progress in neuroscience.

Neurobiological underpinnings of bipolar disorder focusing on findings of diffusion tensor imaging: a systematic review

Objective: To review the available data on diffusion tensor imaging (DTI) of subjects with bipolar disorder (BD), with a particular focus on fractional anisotropy (FA) in white matter (WM) tracts. Methods: The PubMed/MEDLINE database was searched for relevant articles, which were included in a systematic review of the literature. FA reductions and WM abnormalities were divided anatomically into three groups: commissural tracts, association tracts, and projection tracts. Results: Eighteen studies met the inclusion criteria. The corpus callosum was the main impaired commissural tract as demonstrated by FA reductions. Five studies reported FA reductions in the cingulum. Two studies reported decreased FA in the anterior thalamic radiation, and one in the corticospinal tract. Conversely, three studies found increased FA values in WM tracts involved in BD pathophysiology. Conclusion: Despite considerable heterogeneity, these results indicate a direct link between executive cognitive functioning and abnormal WM microstructural integrity of fronto-limbic tracts in patients with remitted BD, providing further evidence of the neuronal disruption that underlies BD symptomatology.

Neural correlates of hallucinations in bipolar disorder

Objective: Approximately one-half of all patients affected by bipolar disorder present with psychotic features on at least one occasion. Several studies have found that alterations in the activity of mesolimbic and prefrontal regions are related to aberrant salience in psychotic patients. The aim of the present study was to investigate the structural correlates of a history of hallucinations in a sample of euthymic patients with bipolar I disorder (BD-I). Methods: The sample consisted of 21 euthymic patients with BD-I and no comorbid axis I DSM-IV-TR disorders. Voxel based morphometry (VBM) was used to compare patients with and without a lifetime history of hallucinations. Preprocessing was performed using the Diffeomorphic Anatomical Registration through Exponentiated Lie Algebra (DARTEL) algorithm for VBM in SPM8. Images were processed using optimized VBM. Results: The main finding of the present study was a reduction in gray matter volume in the right posterior insular cortex of patients with BD-I and a lifetime history of hallucinations, as compared to subjects with the same diagnosis but no history of hallucinations. Conclusions: This finding supports the presence of abnormalities in the salience network in BD patients with a lifetime history of hallucinations. These alterations may be associated with an aberrant assignment of salience to the elements of one’s own experience, which could result in psychotic symptoms.